多发性骨髓瘤驱动基因的筛选

Screening driver mutation genes of multiple myeloma

    摘要
  • 摘要:
      目的  鉴定并比较不同测序方案中多发性骨髓瘤（multiple myeloma，MM）潜在的驱动基因，为探讨MM的发生机制提供研究基础。
      方法  选择两套数据，一套数据为2016年5月至2020年11月苏州大学附属第二医院84例MM患者的基因组靶向突变测序数据，另一套数据从癌症基因组图谱（The Cancer Genome Atlas, TCGA）数据库下载的205例MM全基因组测序数据。在R4.1.0环境下，利用驱动基因识别算法对MM的潜在驱动基因进行挖掘，分析并比较两套数据筛选出的驱动基因及具体突变信息。
      结果  NRAS、KRAS、TP53、IDH1为两套数据共同识别出的驱动基因。两套数据中突变基因在NOTCH、RTK-RAS、Cell-Cycle、TP53、MYC及WNT通路均有富集。显著突变的NRAS、KRAS、TP53和IDH1在两套数据中发生突变的位点无显著性差异。另外，通过靶向突变测序方法，鉴定出MM新的驱动基因，CBL、BCOR和DNMT3A。
      结论  通过本研究获得了MM可能的驱动基因，有助于从基因分子层面揭示MM发生发展机制。

     

    Abstract:
      Objective  The potential driver mutation genes of multiple myeloma (MM) in different sequencing protocols were identified to provide a research basis for exploring the pathogenesis of this disease.
      Methods  This study used two cohorts. A cohort of 84 patients with MM from The Second Affiliated Hospital of Soochow University was subjected to genome-targeted mutation sequencing. The other cohort (205 patients with MM) was selected from The Cancer Genome Atlas (TCGA) using whole-genome sequencing. The potential driver genes of MM were mined using the driver gene identification algorithm in the R4.1.0 environment. Subsequently, the driver genes and mutation spectrum were analyzed.
      Results  NRAS, KRAS, TP53, and IDH1 were identified in the two datasets. Furthermore, the mutated genes in both datasets were enriched in the NOTCH, RTK-RAS, Cell-Cycle, TP53, MYC, and WNT pathways. The recurrent mutation sites in NRAS, KRAS, TP53, and IDH1 showed no significant difference between the two datasets. In addition, new driver genes of MM were identified via targeted mutation sequencing, these are CBL, BCOR, and DNMT3A.
      Conclusions  In this study, we obtained the potential driver genes of MM, which are helpful for revealing the pathogenesis of this disease.

     

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